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Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival.

Sawai H, Yasuda A, Ochi N, Ma J, Matsuo Y, Wakasugi T, Takahashi H, Funahashi H, Sato M, Takeyama H - BMC Gastroenterol (2008)

Bottom Line: The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling.Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05).Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 4678601, Japan. sawai@med.nagoya-cu.ac.jp

ABSTRACT

Background: The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases.

Methods: Sixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls.

Results: PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012).

Conclusion: Our results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients.

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Expression of PTEN in colon cancer specimens. Immunohistochemistry was performed using a monoclonal anti-PTEN antibody (A, C) or negative control antibody (B) on a section sequential to that used in (A). (A) Strong PTEN expression in a representative moderately-differentiated adenocarcinoma specimen from colon cancer patients without associated liver metastasis (×100). (C) Expression of PTEN is not observed in a representative moderately-differentiated adenocarcinoma specimen from colon cancer patients with liver metastasis (×100). (D) Expression of PTEN is not observed in a specimen from metastatic liver tumor, in contrast, PTEN expression is observed in normal liver tissue (×100).
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Figure 1: Expression of PTEN in colon cancer specimens. Immunohistochemistry was performed using a monoclonal anti-PTEN antibody (A, C) or negative control antibody (B) on a section sequential to that used in (A). (A) Strong PTEN expression in a representative moderately-differentiated adenocarcinoma specimen from colon cancer patients without associated liver metastasis (×100). (C) Expression of PTEN is not observed in a representative moderately-differentiated adenocarcinoma specimen from colon cancer patients with liver metastasis (×100). (D) Expression of PTEN is not observed in a specimen from metastatic liver tumor, in contrast, PTEN expression is observed in normal liver tissue (×100).

Mentions: PTEN expression was evaluated in primary colorectal cancer and corresponding liver metastasis specimens. PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases (control, n = 70). In contrast, weak PTEN expression was observed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and PTEN expression was absent in liver metastasis cancer specimens (Figure 1A–D). The marked nuclear staining of PTEN and slight cytoplasmic staining were observed. Weak PTEN expression was significantly associated with advanced TNM stage and lymph node metastasis (Table 2). The actuarial 5-year survival rate of patients with colorectal cancer with liver metastases and positive PTEN expression was 64.4%. In contrast, the actuarial 5-year survival rate of patients with colorectal cancer with liver metastases and negative PTEN expression was 12.7% (Figure 2). In addition, among colorectal cancer patients with liver metastases, there was a significant difference in 5-year survival rate between patients with positive PTEN expression and those with negative PTEN expression (p = 0.012).


Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival.

Sawai H, Yasuda A, Ochi N, Ma J, Matsuo Y, Wakasugi T, Takahashi H, Funahashi H, Sato M, Takeyama H - BMC Gastroenterol (2008)

Expression of PTEN in colon cancer specimens. Immunohistochemistry was performed using a monoclonal anti-PTEN antibody (A, C) or negative control antibody (B) on a section sequential to that used in (A). (A) Strong PTEN expression in a representative moderately-differentiated adenocarcinoma specimen from colon cancer patients without associated liver metastasis (×100). (C) Expression of PTEN is not observed in a representative moderately-differentiated adenocarcinoma specimen from colon cancer patients with liver metastasis (×100). (D) Expression of PTEN is not observed in a specimen from metastatic liver tumor, in contrast, PTEN expression is observed in normal liver tissue (×100).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2611992&req=5

Figure 1: Expression of PTEN in colon cancer specimens. Immunohistochemistry was performed using a monoclonal anti-PTEN antibody (A, C) or negative control antibody (B) on a section sequential to that used in (A). (A) Strong PTEN expression in a representative moderately-differentiated adenocarcinoma specimen from colon cancer patients without associated liver metastasis (×100). (C) Expression of PTEN is not observed in a representative moderately-differentiated adenocarcinoma specimen from colon cancer patients with liver metastasis (×100). (D) Expression of PTEN is not observed in a specimen from metastatic liver tumor, in contrast, PTEN expression is observed in normal liver tissue (×100).
Mentions: PTEN expression was evaluated in primary colorectal cancer and corresponding liver metastasis specimens. PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases (control, n = 70). In contrast, weak PTEN expression was observed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and PTEN expression was absent in liver metastasis cancer specimens (Figure 1A–D). The marked nuclear staining of PTEN and slight cytoplasmic staining were observed. Weak PTEN expression was significantly associated with advanced TNM stage and lymph node metastasis (Table 2). The actuarial 5-year survival rate of patients with colorectal cancer with liver metastases and positive PTEN expression was 64.4%. In contrast, the actuarial 5-year survival rate of patients with colorectal cancer with liver metastases and negative PTEN expression was 12.7% (Figure 2). In addition, among colorectal cancer patients with liver metastases, there was a significant difference in 5-year survival rate between patients with positive PTEN expression and those with negative PTEN expression (p = 0.012).

Bottom Line: The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling.Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05).Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 4678601, Japan. sawai@med.nagoya-cu.ac.jp

ABSTRACT

Background: The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases.

Methods: Sixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls.

Results: PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012).

Conclusion: Our results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients.

Show MeSH
Related in: MedlinePlus